Unraveling the molecular mechanisms underlying intracellular crystal formation

From vision in teleost fish to the spectacular colors reflected from reptiles and crustaceans, intracellular molecular crystals play vital roles in the function of cells and the ecology of organisms. These crystals are formed in specialized cellular vesicles termed iridosomes, where their properties are controlled in ways that cannot be matched by modern technology. Failure to control crystal formation can be deleterious to organisms, obstructing fundamental abilities, such as vision, body temperature regulation, camouflage, and kin recognition, and underlying pathologies such as gout and kidney stones in humans. Exploring the fascinating ability of iridosomes to perform such elaborate chemical and biological processes has thus far been limited by the technical inability to study this complex organelle. To obtain a mechanistic understating of the processes and principles underlying the controlled formation of intracellular crystals, we will harness our unique interdisciplinary set of skills, merging chemistry and cell biology, as well as new approaches combining state-of-the-art imaging and spectroscopy we recently developed. We will use this synergetic experimental platform to identify the molecular players, ultrastructural events (Aim 1) and intracellular mechanisms (Aim 2) underlying intracellular crystal formation in the zebrafish, and then generalize the discoveries to other crystal-forming organisms (Aim 3).Our project will provide a holistic view of the iridosome mechanism of action, the strategies organisms use to form and control bio-molecular crystals, and the biological processes, intracellular organelles, proteins and regulatory mechanisms involved. The obtained mechanistic insight into these processes will advance the understanding of the effect of ocean acidification on crystal formation in marine organisms, and pave the way for developing new biomaterials and much needed therapeutics for pathological crystallization.